Lymphoid system Flashcards
Caseous Lymphadenitis
- species affected
- geographic distribution
Species affected:
◦ Sheep & goats
◦ (Cattle, horses, alpacas, camels, buffalo)
◦ Zoonotic potential > CLA, pneumonia
*Geographical distribution: Worldwide
Caseous Lymphadenitis
- organism characteristics
◦ Corynebacterium pseudotuberculosis
◦ Gram +, diptheroid, facultative anaerobe, facultative intracellular
bacillus
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2 Biotypes
◦ Nitrate negative - sheep & goats
◦ Nitrate positive - Associated with ulcerative lymphangitis in horses/cattle- more common dry
western states (California)
Caseous Lymphadenitis
virulence factors and toxins
Lipid layer outside cell wall
◦ Allows intracellular persistence, resists killing by phagocytes
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Phospholipase D (PLD):
◦ Exotoxin, cytotoxic and partial hemolysin
◦ Promotes local inflammation & necrosis
◦ Damages endothelial cells
◦ Can cause lymphatic thrombosis
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Other toxins:
◦ Sphingomyelinase
◦ Inhibitory factor of Staphylococcal beta-hemolysin
◦ Hemolysis factor
◦ Dermatonecrotoxins
◦ Mouse-lethality toxins
Caseous Lymphadenitis
- pathogenesis
- Skin penetration (inhale, ingest, umbilical)
- Immediate phagocytosis by leukocytes
- Survival in leukocyte
- Transportation to LN → multiplication
- Host cell dies releasing bacteria
- Lymphogenous & hematogenous spread
Caseous Lymphadenitis
◦ Transmission:
Contamination of wounds:
◦ Shearing wounds
◦ Sheep dip
◦ Fighting wounds (goats)
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◦ Traumatized oral mucosa
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◦ Aerosol > Pulmonary abscesses are the primary source of contamination
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◦ All demonstrated transmission through environmental contamination
Caseous Lymphadenitis
◦ Environmental survival:
◦ Shaded areas - up to 20 weeks (shearing sheds)
◦ Soil - up to 8 months
- Brazilian study → semi-arid environment → up to 2 years
◦ On wood surfaces and bedding up to 8 weeks
◦ Commercial sheep dips - 24 hours
◦ Does not replicate outside of host
Caseous Lymphadenitis
- Prevalence
- age
- clinical vs subclinical cases?
Prevalence
◦ Increase with age:
◦ Australian unvaccinated sheep: 3.4% lambs→54% adult ewes
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Many flocks affected
◦ Alberta serology- 50-94% incidence of exposure
◦ Australia 97% flocks (25% of sheep within affected flocks)
◦ 2003 study Quebec 21% culled sheep carcasses
◦ Goats more prevalent: Most Ontario goat herds
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- Clinical cases sporadic (case incidence within flock)
◦ Subclinical cases common
Caseous Lymphadenitis
- how fast can in spread from one animal?
Introduction of infected animal to naive flock
> High incidence of abscesses 2-3 years later
Caseous Lymphadenitis
Clinical signs: (forms, goats vs sheep)
External form (abscessation of superficial lymph nodes) – more common
in goats
◦ Mild to no signs other than LN, unless obstructive
◦ Head/neck most common
◦ Lymph nodes: mandibular, parotid, prescapular, prefemoral
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Internal or visceral form - more common sheep
◦ Deep lymph nodes: mediastinal, bronchial, mesenteric, lumbar
◦ Lung, spleen, liver, kidney
◦ Weight loss, anorexia, depression, fever, cough
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◦ Abscesses lamellated in sheep, creamy/pasty goats
Caseous Lymphadenitis
Diagnosis:
◦ Clinical signs
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◦ CBC not reliable- walled off abscesses
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Serology: ELISA, AGID, SHI (synergistic hemolysis inhibition)
◦ Many tests (high sensitivity)
◦ Specificity poor (because of cross reactivity)
◦ ELISA: sensitivity 96% experimental, 81% natural infection in sheep
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◦ Aspiration of abscess: cytology/culture (ddx– Trueperella pyogenes, Staph. aureus, P.
multocida, anaerobes)
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Post-mortem:
◦ Abscesses in LN, peripheral or visceral or within lung parenchyma.
◦ Localized infection
Caseous Lymphadenitis
Treatment:
Walled off abscesses
◦ Antibiotics have not proven to be of value
◦ Sensitive to many antibiotics in vitro
> Penicillins
> Tulathromycin – subcutaneous, intralesional
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Draining abscesses → environmental contamination
◦ Can be of benefit to individual
◦ Local treatment – flush abscess cavity w dilute iodine or chlorhexidine
Caseous Lymphadenitis
Prevention:
Avoid introduction of an infected animal into the flock.
◦ This relies on a test that correctly identifies the animals.
◦ With reliability issues in the test, repeated testing and staged introduction would be one
method.
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Vaccination: vaccines could protect a clean flock, but are not yet sufficiently reliable
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Control:
◦ Eradication: identification and removal of infected animals.
Caseous Lymphadenitis
Vaccination:
- efficacy?
◦ Reduces severity of signs in endemic flocks
◦ Reduces economic loss
◦ Cannot use to eradicate the disease
◦ Number of vaccines available
Bovine Leukosis - other names?
Enzootic Leukosis
Sporadic Leukosis
etc….
Enzootic Bovine Leukosis
- type of disease
- etiology
- tissues affected
- result
- Neoplastic disease
- Induced by a retrovirus: BLV
- Almost any tissue affected
- Highly fatal once clinical
- Viral infection ≠ lymphoma
Enzootic Bovine Leukosis
- pathogen
Etiology: BLV – oncogenic type-C virus
- retroviridae
- enveloped virus
Enzootic Bovine Leukosis
- infects what cells?
- antibodies?
- detection of infection?
- duration?
- Virus persists mainly in B-lymphocytes
◦ Also monocytes, macrophages in pro-viral cell-associated, non-active form - Antibodies produced but non-protective
- Seropositivity reliably indicates infection > In animals over 6 months
- Infection considered permanent
Enzootic Bovine Leukosis
- epidemiology: who gets it? pattern?
Epidemiology: (clinical disease)
* not well understood
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* Herd size and infection rate (positive correlation?)
* Higher rate dairy herds > Herd size, age, genetics?
* Higher rate certain families (BoLA-type) > Predisposition through antigens of Major Histocompatibility Complex (MHC)
*No seasonal pattern for clinical lymphosarcoma
Enzootic Bovine Leukosis
Factors influencing clinical disease
◦ Age
◦ Level of infection in herd
◦ Opportunities for contact
◦ Status of dam
◦ Inter-current disease/stress
◦ Genetic factors
Enzootic Bovine Leukosis
Transmission:
Horizontal (primary mode: ≈18 months)
◦ True natural transmission - Cow-to-cow spread
◦ Transmission by blood-contaminated equipment
> Blood collection, tattooing, ear tags, dehorning, rectal palpation
> AI – passage from semen of infected bulls not shown
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Vertical (less likely)
◦ Maternal antibodies in milk may be protective
◦ In utero or during calving (4-10% of positive cases)
Enzootic Bovine Leukosis
Disease prevalence? what diseases?
◦ Seropositive: Variable numbers reported
> Farm level high (as many as 80% positive)
> 5-40% cattle reported as positive
> Prevalence increased after 24 months-of-age
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Clinically affected:
◦ Persistent Lymphocytosis (PL): approx 30% of seropositive animals
◦ Lymphoma: 1-5% of seropositive animals
Enzootic Bovine Leukosis
- what determines if an animal will express disease?
◦ Influenced by genetic susceptibility
◦ Explains why so few animals have clinical disease
◦ Explains why slow disease spread
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Variability animal to animal
◦ Multifactorial effect on expression of disease
Enzootic Bovine Leukosis
- as a retrovirus, what does it rely on the host for?
◦ Latency, relies on cell for replication, cell transformation
Enzootic Bovine Leukosis
- affects what cells, mostly?
- two main disease presentations?
B-Cells
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Persistent lymphocytosis (count variable, up to 100 x109/L)
◦ Subclinical lymphoproliferative state
◦ ?pre-lymphosarcoma?
◦ Expression of tumor-associated antigen on circulating lymphocytes
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Multicentric lymphosarcoma
◦ Adults >2 years of age
◦ Most 4-8 years
◦ Sporadic in herd
Enzootic Bovine Leukosis
Multi-centric lymphosarcoma
- clinical signs
◦ Variable: depends on organs affected
◦ General: weight loss, reduced production
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Frequent target organs:
◦ Lymph node enlargement: external or internal
◦ Thoracic LN: obstruction to venous drainage
◦ Retrobulbar masses may cause exophthalmus
◦ Abomasal wall: diarrhea, melena, outflow obstruction
◦ Myocardium (right atrium): congestive heart failure, arrhythmias
◦ Renal, uterus, skeletal muscle, retropharyngeal LN
◦ Meninges, posterior paralysis
Enzootic Bovine Leukosis
- Dx for persistent lymphocytosis and multicentric lymphosarcoma diseases
Persistent lymphocytosis
◦ CBC: cell counts, ratios >25% immature cells, morphology
◦ False positives common
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Multicentric lymphosarcoma
◦ Any adult with lymphadenopathy
◦ LN aspirate (not reliable), ddx reactive lymph node
◦ CBC not rewarding
◦ Serology and post-mortem
Enzootic Bovine Leukosis
Testing
◦ ELISA – more sensitive than traditional AGID
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◦ PCR very reliable, nested PCR
> Useful in eradication programs
> Expensive
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◦ Combined ELISA/PCR
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◦ Loop-mediated isothermal amplification (LAMP) assay
> As sensitive as single PCR, do not need a thermocycler
Enzootic Bovine Leukosis
◦ Agar gel immunodiffusion (AGID) method for testing, pros and cons?
◦ Sensitivity 99.8%, specificity 98.5%
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False negatives
◦ Some animals do not develop high levels of AB
◦ AB not detectible for up to 20 days post-infection
◦ Post-calving sequestration - mammary gland
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False positives
◦ First 2-7 months after birth from positive dam
◦ Post blood/plasma transfusion
Enzootic Bovine Leukosis
Control
- some countries attempting eradication
- already eradicated in a number of EU countries
- no vaccines
Sporadic Bovine Leukosis
- what is this?
- cells affected?
Group of neoplastic diseases of the lymphatic tissue not associated with
BLV:
1. Juvenile multi-centric lymphoma
2. Thymic lymphoma
3. Cutaneous lymphoma
4. Atypical Forms
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B- or T-cell lineage
Sporadic Bovine Leukosis
> Juvenile lymphoma
- age affected, prevalence
- disease course
- clinical signs
- pathogenesis
◦ Age: 3 - 6 months-of-age (range 1-month to 3-years-of age)
◦ Prevalence unknown, considered rare
◦ Rapid course - weeks, often sudden onset
◦ Clinical signs:
◦ Weight loss, depression, anemia, lymphadenopathy, variable signs depending on organ involvement (lymph nodes, liver, kidney, spleen, uterus, heart, spinal column
nodes)
◦ Bone marrow infiltration → anemia, leukemia
◦ BLV independent (ie. not virus-associated)
Sporadic Bovine Leukosis
> Cutaneous lymphoma
- age
- lesions, locations
- progression
◦ Age: 1-3 years-of-age
◦ Dermal lesions
◦ Usually dorsum, hind limbs, perineal areas
◦ May progress to multicentric (may have organ involvement)
◦ Lesions: 3 cm, necrotic centers, May regress and recur
Sporadic Bovine Leukosis
> Thymic lymphoma
- prevalence
- breeds
- age
- signs
◦ Rare
◦ Beef breeds more common
◦ Age: 6 months - 2 years (range: newborn to 4-years-old)
◦ Signs associated with mass in mediastinum > Obstruction of venous return from front end
◦ Jugular distension, edema, may have thoracic fluid > Interference with respiration, eructation (bloat)
Sporadic Bovine Leukosis
> Atypical Forms
- what are these? what can they affect?
(individual cases in the literature)
◦ Muscle
◦ Trachea, skin
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Alpaca:
◦ Mandibular masses, weight loss
◦ Disseminated small lymphoma – pancreas, kidney, liver, omentum, caudal vena cava
◦ BLV proviral DNA detect in some tissues
Bovine Immunodeficiency
Virus
- pathogen?
- similar to?
- disease?
- associations?
◦ Family – Retroviridae
◦ Genus - Lentivirus
◦ BIV - similar to human, simian, feline immunodeficiency viruses.
Also EIA
◦ Does not appear to cause clinical disease
◦ May be associated with lymphadenopathy, lymphocytosis, decreased milk
production, CNS disease, weakness.
Bovine Immunodeficiency
Virus
- prevalence?
- production parameters?
- management?
◦ Prevalence low but not uncommon
◦ May be associated with decreased milk production
◦ Management – decrease cattle contact may decrease spread
